1. Field of the Invention
This invention relates in general to 5-hydroxytryptophan derivatives and their use as analgesic compounds. More particularly, it relates to N-substituted derivatives of 5-hydroxytryptophan and dimers thereof.
2. Description of the Prior Art
5-Hydroxytryptophyl peptides of similar structure are described in two literature publications: H. Tamir and M. Wilchek, J. Neurochem 32, 593-598 (1979) and H. Tamir et al, Life Sciences, Vol. 25, pp 655-664 (1979).
In the first publication, the peptides 5HTP-5HTP amide; N-acetyl-5HTP-5HTP amide and the derivative 5HTP methyl ester are described and their effect on the binding of serotonin to serotonin-binding protein (SBP) is disclosed.
The second reference describes the analgesic effects of N-acetyl-5HTP-5HTP amide, one of the compounds recited in the first publication.
As is evident by visual inspection, the compounds disclosed and claimed herein differ structurally from the N-acetyl derivative recited above in that inter alia, substituent R of compounds represented by formula I or II has a minimum carbon chain of two carbons, and preferably at least three. Functionally, this difference provides unexpectedly, significantly different properties. The N-acetyl derivative, only when injected intraventricularly, affects pain threshold, but it does not pass through the blood-brain barrier. It has no effect when injected intraperitoneally (I.P.) even at very high doses.
In contrast, the compounds disclosed and claimed herein successfully reach the brain by passing through the blood-brain barrier. As a result, the instant compounds significantly and lastingly raise the pain threshold of pain without affecting activity when administered intraperitoneally.
Moreover, the instant compounds are believed to be non-addicting, have no cross-tolerance with morphine and appear to have little or no toxic effect.
Because of these unusual characteristics, the compounds of this invention fulfill a real need in this art and the industry in general.